The total syntheses of medicinally active compounds are important pursuits in the field of biomedical science. In line with our interest in the efficient total synthesis of biologically active natural products, we are pursuing a program of research directed toward the development of new carbon-carbon bond construction reactions. The reactions will simplify the assembly of the carbon backbone in a variety of natural products. The proposed research specifically examines intramolecular iron(O) catalyzed (4+2)- and (4+4)-ene reactions, which are emerging as valuable new methodologies for the preparation of functionalized carbo- and heterocyclic ring systems. The reactions under investigation include the iron(O) catalyzed ene coupling of 1,3-dienes to 2-substituted acrylate esters and to allylic ethers. The cyclizations of these substrates proceed with novel aspects of regio- and stereochemical control. In particular these reactions proceed with exceptional levels of stereoinduction and define a new strategy for the asymmetri synthesis of carbo- and heterocyclic ring systems. Under the period of this grant we propose to continue our studies on these highly successful carbocyclization reactions. Our goal is to make accessible, through iron-mediated stereoselective synthesis, key ring systems which are common subunits within the structures of biologically active natural products. The specific aims of our proposed research are to use catalytic iron-mediated carbocyclization reactions to: 1) accomplish the stereoselective synthesis of highly functionalized 5- and 6-membered ring carbocycles, 5- and 6-membered ring oxygen- and nitrogen- heterocycles, and medium-ring systems; 2) accomplish the steroselective synthesis of common fused-bicyclic ring systems; 3) prepare chiral non-racemic carbocyclic and heterocyclic ring systems in a stereocontrolled fashion through the use of recoverable chiral auxiliaries 4) defined substrates for new, but mechanistically related, carbocyclization reactions; and 5) understand in detail the origins of metal-dependent reaction selectivities.